Raltegravir Racial Analysis Marks an Evolution in HIV Drug Studies

Some may think the logic is straightforward: If one is conducting clinical trials for a drug, one would want the study population to resemble the group of people most likely to receive that drug. Until relatively recently, however, HIV drug trials in the U.S. tended to be poorly reflective of the full breadth of the real-world target population; clinical trial volunteers have tended to skew heavily white and male.

Kathleen Squires, M.D., the director of the Division of Infectious Diseases at Thomas Jefferson University, has been at the forefront of efforts to change this longstanding trend. In a poster presented at ICAAC 2014, Squires and colleagues explore the results of one recent effort along these lines: a post-approval analysis of the integrase inhibitor raltegravir (Isentress) focusing particularly on African Americans and women.

Our editorial director Myles Helfand caught up with Dr. Squires at her poster to discuss the study and its findings, as well as the role of such studies in the future of HIV drug research. Dr. Squires began with a walkthrough of the poster.

We were interested in looking at raltegravir, and [at the] efficacy and safety of this drug by race. One of the reasons we were interested in it -- well, there are actually two reasons. One, because analyses of other drug trials by race have shown that the drug has been underperforming in blacks. So, obviously, we were interested in that question.

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I had also done a gender analysis, looking at raltegravir by gender. Gender is confounded by race, especially in women in the United States, because of the fact that the majority of women who have HIV infection in the United States are black. So I wanted to look at this drug and see what data was available across clinical trials.

What we did here is, we took the two largest treatment-naive trials for this drug, which were the STARTMRK trial and the QDMRK trial, and took patients who had received raltegravir, 400 mg twice a day -- which is the standard dose -- and simply broke those patients out by black, or not black, race. That's self-identified. Then we looked at the characteristics of these patients.

What we found, in terms of the baseline characteristics, is that, as we might have expected, a higher proportion of women in this study were black. We also saw that a higher proportion of black patients had non-clade B virus. That's because these were international trials. We also saw that both the mean and the median CD4 counts were lower in black patients than in white patients. That's probably a reflection of the stage of disease that the patients came into the study with.

Then we looked at the off-treatment rates, which were similar, although there was a higher off-treatment rate for blacks than whites. It's not because of lack of efficacy; there are a number of other reasons why patients came out of the trial.

Other studies have tried to pick at that a little bit, to try to get at some of the socioeconomic or infrastructural kinds of reasons.

Right. The limiting step there is what data [were] collected on the study. If you don't have it, you don't have it.

[Next,] we looked at the percentage of patients who were able to achieve viral loads of less than 50 copies at 48 weeks, and the change in baseline for CD4 cell counts. What we saw is that very similar proportions of black patients and non-black patients achieved virological efficacy, and that the rises in CD4 cell counts were about the same -- although they were a bit higher, since they started higher, in non-blacks. It was a little bit higher at 48 weeks.

In terms of side effects, there really wasn't any difference in the rate of side effects. The one difference that we saw, although it wasn't statistically significant, is that decreased ANC [absolute neutrophil count] was more common among black patients than among non-black patients. One thing that we know about this: In general -- and a lot of these patients are coming from sub-Saharan Africa -- but we know that there's such a thing as neutropenia; and we do see it more commonly in black patients than in non-[black patients]. So I think that's what's going on here, rather than an effect of the drug.

In terms of people coming off of the study due to drug-related [adverse events], there was no difference at all between races.

[This] is an exploratory analysis -- in other words, it's a post-hoc analysis -- but there weren't really any differences in terms of efficacy and safety between races. There were no signals. As I said, the rate of treatment discontinuation was higher among black patients, but that wasn't because of lack of efficacy or increased rate of adverse events.

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